The overall goal of this research is to study the activation of particular genes in diseased and normal cells in order to understand which genes may play important roles in the development of malignancies, autoimmune diseases and normal differentiation. We have concentrated on the expression of "oncogenes," especially abl, bcl-2, myc, myb, Pvt-1, raf, ras and rel, as well as immunoglobulin and T-cell receptor genes in tumors that represent immortalized lines of lymphocytes or myeloid cells at different stages of differentiation. The deregulated expression of the myc oncogene has been clearly shown to be essential to the induction of plasma cell tumors, but how "variant" plasmacytomas with rcpt(6;15) translocations involving the Pvt-1 gene, which is 200-300 kb 3' of c-myc, also deregulate c-myc expression remains unknown. We have cloned several cDNAs for mouse Pvt-1, which has, for the first time, permitted the identification of mRNA from this gene in normal mouse tissues and tumors. "Variant" plasmacytomas have elevated levels of Pvt-1 transcripts which are also truncated due to the chromosomal translocation. The v-abl oncogene has been found to cooperate with over-expressed c-myc in a retrovirus (ABL-MYC) which induces plasmacytomas more rapidly than previously reported and, for the first time, in 100% of adult mice, even in the absence of pristane priming. The rapidity of this induction has permitted the production of antigen-targeted myeloma proteins by ABL-MYC induction of plasmacytomas in immunized mice. An important family of protein kinases, Protein Kinase C (PKC), is being studied for its possible role in tumorigenesis. We have shown that the members of this gene family are differentially expressed in tumors of hemopoietic cell and that there is at least one undescribed form of PKC expressed in myeloid tumors. Alternatively spliced transcripts of the myb proto-oncogene have been observed in normal and tumor cells in man as well as mouse. An important difference between the species is that the alternate forms of human c-myb result in truncated protein isoforms instead of the elongated ones expected in mice.